Project Summary/Abstract Protein dynamics is essential for its biological function. With integration of molecular biology, state-of-the-art time-resolved laser spectroscopy and computation simulations, the biological dynamics now can be studied from the initial ultrafast motions to longtime fluctuations on the most fundamental level. The molecular mechanisms thus can be revealed. We have recently investigated the dynamics and mechanism of water-protein interactions and elucidated the fundamental water-protein coupling motions occurring on the picosecond time scales, an ideal timescale to bridge the gap between ultrafast bulk-water motions and slow protein fluctuations. The understanding of biological water is significant to a variety of biological activities such as protein-ligand/drug recognition and enzymatic catalysis. In another direction, we also made significant advances on repair of UV-damaged DNA and mapped out most repair processes in real time, including a series of ultrafast elementary reactions. We will elucidate the complete repair photocycles at the local molecular level over a wide time scale from femtoseconds to milliseconds and provide a molecular basis for potential applications such as rational drug design for curing skin cancer. In this new effort, we will build a novel time-resolved method to explore complex systems over a wide time range on two major areas of (1) investigating interfacial water dynamics at protein-DNA and protein-protein complexes to gain the deep understanding of binding properties and dynamic fluctuations of complexes for biological functions and (2) examining two important photomachines of photoreceptors (blue-light cryptochrome, UV-light receptor UVR8 and red-light phytochrome) and photoenzyme photolyases. By systematic investigations of these dynamics over a wide time range, we will uncover the entire process of initial signal transduction and reveal the reaction mechanisms and photocycles of phytochrome and UVR8. The new knowledge obtained from these efforts on biological-water dynamics and photoreceptor/photoenzymes photocycles is significant to protein properties, dynamics, and functions involving protein-DNA/protein complexes and signal transduction processes, and more importantly, is critical to practical applications of drug design for a series of diseases such as mental disorder.